title: Molecular pathology and prostate cancer therapeutics: from biology to bedside.
abstract: Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men and has an extremely heterogeneous clinical behaviour. The vast majority of PCas are hormonally driven diseases in which androgen signalling plays a central role. The realization that castration-resistant prostate cancer (CRPC) continues to rely on androgen signalling prompted the development of new, effective androgen blocking agents. As the understanding of the molecular biology of PCas evolves, it is hoped that stratification of prostate tumours into distinct molecular entities, each with its own set of vulnerabilities, will be a feasible goal. Around half of PCas harbour rearrangements involving a member of the ETS transcription factor family. Tumours without this rearrangement include SPOP mutant as well as SPINK1-over-expressing subtypes. As the number of targeted therapy agents increases, it is crucial to determine which patients will benefit from these interventions and molecular pathology will be key in this respect. In addition to directly targeting cells, therapies that modify the tumour microenvironment have also been successful in prolonging the lives of PCa patients. Understanding the molecular aspects of PCa therapeutics will allow pathologists to provide core recommendations for patient management.
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Daniel Nava
authors.initials: DN
authors.lastname: Rodrigues
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Butler
authors.forename: David Lorente
authors.initials: DL
authors.lastname: Estelles
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects; D055808:Drug Discovery; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D057170:Translational Research, Biomedical; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors
keywords: castration-resistant; molecular pathology; prostate cancer; targeted therapy